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18 pages, 2315 KiB  
Article
Cannabinoid Receptors in the Horse Lateral Nucleus of the Amygdala: A Potential Target for Ameliorating Pain Perception, Stress and Anxiety in Horses
by Cristiano Bombardi, Giulia Salamanca, Claudio Tagliavia, Annamaria Grandis, Rodrigo Zamith Cunha, Alessandro Gramenzi, Margherita De Silva, Augusta Zannoni and Roberto Chiocchetti
Int. J. Mol. Sci. 2025, 26(15), 7613; https://doi.org/10.3390/ijms26157613 - 6 Aug 2025
Abstract
The amygdala is composed of several nuclei, including the lateral nucleus which is the main receiving area for the input from cortical and subcortical brain regions. It mediates fear, anxiety, stress, and pain across species. Evidence suggests that the endocannabinoid system may be [...] Read more.
The amygdala is composed of several nuclei, including the lateral nucleus which is the main receiving area for the input from cortical and subcortical brain regions. It mediates fear, anxiety, stress, and pain across species. Evidence suggests that the endocannabinoid system may be a promising target for modulating these processes. Cannabinoid and cannabinoid-related receptors have been identified in the amygdala of rodents, carnivores, and humans, but not in horses. This study aimed to investigate the gene expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R), transient receptor potential vanilloid 1 (TRPV1), and peroxisome proliferator-activated receptor gamma (PPARγ) within the lateral nucleus of six equine amygdalae collected post mortem from an abattoir using quantitative real-time PCR, cellular distribution, and immunofluorescence. mRNA expression of CB1R and CB2R, but not TRPV1 or PPARγ, was detected. The percentage of immunoreactivity (IR) was calculated using ImageJ software. Cannabinoid receptor 1 immunoreactivity was absent in the somata but was strongly detected in the surrounding neuropil and varicosities and CB2R-IR was observed in the varicosities; TRPV1-IR showed moderate expression in the cytoplasm of somata and processes, while PPARγ-IR was weak-to-moderate in the neuronal nuclei. These findings demonstrate endocannabinoid system components in the equine amygdala and may support future studies on Cannabis spp. molecules acting on these receptors. Full article
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18 pages, 3229 KiB  
Article
AMPK-Targeting Effects of (−)-Epicatechin Gallate from Hibiscus sabdariffa Linne Leaves on Dual Modulation of Hepatic Lipid Accumulation and Glycogen Synthesis in an In Vitro Oleic Acid Model
by Hui-Hsuan Lin, Pei-Tzu Wu, Yu-Hsuan Liang, Ming-Shih Lee and Jing-Hsien Chen
Int. J. Mol. Sci. 2025, 26(15), 7612; https://doi.org/10.3390/ijms26157612 - 6 Aug 2025
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant (p < 0.01) decrease in oxidative stress by 83%, and a marked (p < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes. Full article
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18 pages, 2476 KiB  
Article
Fucoidan Modulates Osteoarthritis Progression Through miR-22/HO-1 Pathway
by Tsung-Hsun Hsieh, Jar-Yi Ho, Chih-Chien Wang, Feng-Cheng Liu, Chian-Her Lee, Herng-Sheng Lee and Yi-Jen Peng
Cells 2025, 14(15), 1208; https://doi.org/10.3390/cells14151208 - 6 Aug 2025
Abstract
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. [...] Read more.
Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article
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16 pages, 2440 KiB  
Article
Dog–Stranger Interactions Can Facilitate Canine Incursion into Wilderness: The Role of Food Provisioning and Sociability
by Natalia Rojas-Troncoso, Valeria Gómez-Silva, Annegret Grimm-Seyfarth and Elke Schüttler
Biology 2025, 14(8), 1006; https://doi.org/10.3390/biology14081006 - 6 Aug 2025
Abstract
Most research on domestic dog (Canis familiaris) behavior has focused on pets with restricted movement. However, free-ranging dogs exist in diverse cultural contexts globally, and their interactions with humans are less understood. Tourists can facilitate unrestricted dog movement into wilderness areas, [...] Read more.
Most research on domestic dog (Canis familiaris) behavior has focused on pets with restricted movement. However, free-ranging dogs exist in diverse cultural contexts globally, and their interactions with humans are less understood. Tourists can facilitate unrestricted dog movement into wilderness areas, where they may negatively impact wildlife. This study investigated which stimuli—namely, voice, touch, or food—along with inherent factors (age, sex, sociability) motivate free-ranging dogs to follow a human stranger. We measured the distance (up to 600 m) of 129 free-ranging owned and stray dogs from three villages in southern Chile as they followed an experimenter who presented them one of the above stimuli or none (control). To evaluate the effect of dog sociability (i.e., positive versus stress-related or passive behaviors), we performed a 30 s socialization test (standing near the dog without interacting) before presenting a 10 s stimulus twice. We also tracked whether the dog was in the company of other dogs. Each focus dog was video-recorded and tested up to three times over five days. Generalized linear mixed-effects models revealed that the food stimulus significantly influenced dogs’ motivation to follow a stranger, as well as a high proportion of sociable behaviors directed towards humans and the company of other dogs present during the experiment. Juveniles tended to follow a stranger more than adults or seniors, but no effects were found for the dog’s sex, whether an owner was present, the repetition of trials, the location where the study was performed, or for individuals as a random variable. This research highlights that sociability as an inherent factor shapes dog–stranger interactions in free-ranging dogs when food is given. In the context of wildlife conservation, we recommend that managers promote awareness among local communities and tourists to avoid feeding dogs, especially in the context of outdoor activities close to wilderness. Full article
(This article belongs to the Special Issue Biology, Ecology, Management and Conservation of Canidae)
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16 pages, 1651 KiB  
Article
Standardization of Germinated Oat Extracts and Their Neuroprotective Effects Against Aβ1-42 Induced Cytotoxicity in SH-SY5Y Cells
by Yu-Young Lee, In-Su Na, Jeong-Eun Kim, Jae-Gwang Song, Chae-Eun Han, Hyung-Wook Kim and Soon-Mi Shim
Molecules 2025, 30(15), 3291; https://doi.org/10.3390/molecules30153291 - 6 Aug 2025
Abstract
The present study aimed to standardize germinated oat extracts (GOEs) by profiling avenanthramides (AVNs) and phenolic acids and evaluate their neuroprotective effects against Aβ1-42-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells. GOEs were standardized to contain 1652.56 ± 3.37 µg/g dry weight [...] Read more.
The present study aimed to standardize germinated oat extracts (GOEs) by profiling avenanthramides (AVNs) and phenolic acids and evaluate their neuroprotective effects against Aβ1-42-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells. GOEs were standardized to contain 1652.56 ± 3.37 µg/g dry weight (dw) of total AVNs, including 468.52 ± 17.69 µg/g AVN A, 390.33 ± 10.26 µg/g AVN B, and 641.22 ± 13.89 µg/g AVN C, along with 490.03 ± 7.83 µg/g dw of ferulic acid, using a validated analytical method. Treatment with AVN C and GOEs significantly inhibited Aβ1-42-induced cytotoxicity (p < 0.05). Furthermore, both AVNs and GOEs markedly reduced Aβ1-42-induced reactive oxygen species (ROS) generation in SH-SY5Y cells, showing significant scavenging activity at concentrations of 25 μg/mL (AVNs) and 50 μg/mL (GOEs) (p < 0.05). RT-PCR analysis revealed that AVNs and GOEs effectively downregulated the expression of inflammation- and apoptosis-related genes triggered by Aβ1-42 exposure. These findings suggest that GOEs rich in AVNs may serve as a potential functional ingredient for enhancing memory function through the inhibition of neuroinflammation and oxidative stress. Full article
(This article belongs to the Special Issue Bioactive Compounds in Foods and Their By-Products)
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51 pages, 2918 KiB  
Review
Therapeutic Applications and Mechanisms of Superoxide Dismutase (SOD) in Different Pathogenesis
by Shehwaz Anwar, Tarique Sarwar, Amjad Ali Khan and Arshad Husain Rahmani
Biomolecules 2025, 15(8), 1130; https://doi.org/10.3390/biom15081130 - 5 Aug 2025
Abstract
An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O2– is produced by numerous biochemically relevant redox processes and is thought [...] Read more.
An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defenses is known as oxidative stress, and it is implicated in a number of diseases. The superoxide radical O2– is produced by numerous biochemically relevant redox processes and is thought to play role in diseases and pathological processes, such as aging, cancer, membrane or DNA damage, etc.; SOD, or superoxide dismutase, is essential for reducing oxidative stress. As a result, the elimination of ROS by SOD may be a useful disease prevention tactic. There have been reports of protective effects against neurodegeneration, apoptosis, carcinogenesis, and radiation. Exogenous SODs’ low bioavailability has drawn criticism. However, this restriction might be removed, and interest in SOD’s medicinal qualities increased with advancements in its formulation. This review discusses the findings of human and animal studies that support the benefits of SOD enzyme regulation in reducing oxidative stress in various ways. Additionally, this review summarizes contemporary understandings of the biology of Cu/Zn superoxide dismutase 1 (SOD1) from SOD1 genetics and its therapeutic potential. Full article
(This article belongs to the Topic Enzymes and Enzyme Inhibitors in Drug Research)
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14 pages, 1058 KiB  
Article
Sex- and Age-Specific Utilization Patterns of Nuclear Medicine Procedures at a Public Tertiary Hospital in Jamaica
by Tracia-Gay Kennedy-Dixon, Mellanie Didier, Fedrica Paul, Andre Gordon, Marvin Reid and Maxine Gossell-Williams
Hospitals 2025, 2(3), 21; https://doi.org/10.3390/hospitals2030021 - 5 Aug 2025
Abstract
Understanding the utilization patterns of nuclear medicine (NM) services is essential for optimizing resource allocation and service provision. This study aimed to address the regional evidence gap by reporting the demand for NM services by sex and age at a public hospital in [...] Read more.
Understanding the utilization patterns of nuclear medicine (NM) services is essential for optimizing resource allocation and service provision. This study aimed to address the regional evidence gap by reporting the demand for NM services by sex and age at a public hospital in Jamaica. This was a non-experimental, retrospective study of NM scans that were completed at the University Hospital of the West Indies from 1 June 2022 to 31 May 2024. While all scans were reported in the descriptive totals, for patients with multiple scans during the study period, only the data from the first visit was used in the inferential statistical analysis. This was performed with the IBM SPSS (version 29.0) software and involved the use of chi-square goodness of fit and multinomial logistic regression. A total of 1135 NM scans for 1098 patients were completed (37 patients had more than one scan); 596 (54.3%) were female and 502 (45.7%) were male, with the ages ranging from 3 days to 94 years old. Among the female patients, there was a greater demand in the ≥60 years age group for cardiac amyloid scans (χ2 = 6.40, p < 0.05), while females 18–59 years had a greater demand for thyroid scans (χ2 = 7.714, p < 0.05) and bone scans (χ2 = 3.904, p < 0.05). On the other hand, significantly more males in the ≥60 age group presented for cardiac amyloid (χ2 = 4.167; p < 0.05) and bone scans (χ2 = 145.79, p < 0.01). Males were significantly less likely to undergo a thyroid scan than females (p < 0.01, OR = 0.072, 95% CI: 0.021, 0.243) while individuals aged 18–59 years were more likely to undergo this scan than patients aged 60 or older (p = 0.02, OR = 3.565, 95% CI: 1.258, 10.104). Males were more likely to do a cardiac amyloid scan (p < 0.05, OR = 2.237, 95% CI: 1.023, 4.891) but less likely to undergo a cardiac rest/stress test than females (p = 0.02, OR = 0.307, 95% CI: 0.114, 0.828). Prolonged life expectancy and an aging population have the potential to impact NM utilization, thus requiring planning for infrastructure, equipment, work force, and supplies. Cancer-related and cardiovascular indications are a top priority at this facility; hence, age- and sex-specific analysis are useful in establishing models for policy makers with regard to the allocation of economic and human resources for the sustainability of this specialized service. Full article
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26 pages, 884 KiB  
Review
Harnessing Seed Endophytic Microbiomes: A Hidden Treasure for Enhancing Sustainable Agriculture
by Ayomide Emmanuel Fadiji, Adedayo Ayodeji Lanrewaju, Iyabo Olunike Omomowo, Fannie Isela Parra-Cota and Sergio de los Santos-Villalobos
Plants 2025, 14(15), 2421; https://doi.org/10.3390/plants14152421 - 4 Aug 2025
Abstract
Microbes perform diverse and vital functions in animals, plants, and humans, and among them, plant-associated microbiomes, especially endophytes, have attracted growing scientific interest in recent years. Numerous plant species thriving in diverse environments have been shown to host endophytic microbes. While endophytic bacteria [...] Read more.
Microbes perform diverse and vital functions in animals, plants, and humans, and among them, plant-associated microbiomes, especially endophytes, have attracted growing scientific interest in recent years. Numerous plant species thriving in diverse environments have been shown to host endophytic microbes. While endophytic bacteria commonly colonize plant tissues such as stems, roots, and leaves, seed-associated endophytes generally exhibit lower diversity compared to those in other plant compartments. Nevertheless, seed-borne microbes are of particular importance, as they represent the initial microbial inoculum that influences a plant’s critical early developmental stages. The seed endophytic microbiome is of particular interest due to its potential for vertical transmission and its capacity to produce a broad array of phytohormones, enzymes, antimicrobial compounds, and other secondary metabolites. Collectively, these functions contribute to enhanced plant biomass and yield, especially under abiotic and biotic stress conditions. Despite their multifaceted roles, seed microbiomes remain underexplored in plant ecology, and their potential benefits are not yet fully understood. This review highlights recent advances in our understanding of the diversity, community composition, mechanisms of action, and agricultural significance of seed endophytic microbes. Furthermore, it synthesizes current insights into how seed endophytes promote plant health and productivity and proposes future research directions to fully harness their potential in sustainable agriculture. Full article
(This article belongs to the Section Plant Protection and Biotic Interactions)
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21 pages, 2139 KiB  
Review
New Perspectives on Nutraceutical Insulin Sensitizing Agents in the Treatment of Psoriasis and Other Dermatological Diseases
by Pietro Morrone, Francesca Caroppo, Alberto De Pedrini, Alessandro Colletti and Germano Baj
Int. J. Mol. Sci. 2025, 26(15), 7538; https://doi.org/10.3390/ijms26157538 - 4 Aug 2025
Abstract
Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review [...] Read more.
Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article
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36 pages, 1202 KiB  
Article
Exploring Service Needs and Development Strategies for the Healthcare Tourism Industry Through the APA-NRM Technique
by Chung-Ling Kuo and Chia-Li Lin
Sustainability 2025, 17(15), 7068; https://doi.org/10.3390/su17157068 - 4 Aug 2025
Abstract
With the arrival of an aging society and the continuous extension of the human lifespan, the quality of life has not improved in a corresponding manner. People’s demand for happiness and health is increasing. As a result, a model emerged that integrates tourism [...] Read more.
With the arrival of an aging society and the continuous extension of the human lifespan, the quality of life has not improved in a corresponding manner. People’s demand for happiness and health is increasing. As a result, a model emerged that integrates tourism and medical services, which is health tourism. This growing demand has prompted many service providers to see it as a business opportunity and enter the market. Tourism can help travelers release work stress and restore physical and mental balance; meanwhile, health check-ups and disease treatment can help them regain health. Consumers have long favored health and medical tourism because it helps relieve stress and promotes overall well-being. As people age, some consumers experience a gradual decline in physical functions, making it difficult for them to participate in regular travel services provided by traditional travel agencies. Therefore, this study aims to explore the service needs of health and medical tourism customers (tourists/patients) and the interrelationships among these service needs, so that health and medical tourism service providers can develop more customized and diversified services. This study identifies four key drivers of medical tourism services: medical services, medical facilities, tour planning, and hospitality facilities. This study uses the APA (attention and performance analysis) method to assess each dimension and criterion and utilizes the DEMATEL method with the NRM (network relationship map) to identify network relationships. By combining APA and NRM techniques, this study develops the APA-NRM technique to evaluate adoption strategies and identify suitable paths for health tourism services, providing tailored development strategies and recommendations for service providers to enhance the service experience. Full article
(This article belongs to the Special Issue Inclusive Tourism and Its Place in Sustainable Development Concepts)
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18 pages, 640 KiB  
Article
Suicidal Ideation, Lifestyle Factors, and Burnout Syndrome Among Spanish Professionals in Implant Dentistry: A Survey-Based Cross-Sectional Observational Study
by Ángel-Orión Salgado-Peralvo, Naresh Kewalramani, Eugenio Velasco-Ortega, José López-López, Álvaro Jiménez-Guerra, Loreto Monsalve-Guil, Jesús Moreno-Muñoz, José-Luis Rondón-Romero, Iván Ortiz-García and Enrique Núñez-Márquez
J. Clin. Med. 2025, 14(15), 5486; https://doi.org/10.3390/jcm14155486 - 4 Aug 2025
Abstract
Background: Burnout syndrome (BS) is an occupational phenomenon resulting from chronic workplace stress that has not been successfully managed. Although there are underlying causes associated with personal attributes, it is generally linked to external factors within the work environment. The aim of [...] Read more.
Background: Burnout syndrome (BS) is an occupational phenomenon resulting from chronic workplace stress that has not been successfully managed. Although there are underlying causes associated with personal attributes, it is generally linked to external factors within the work environment. The aim of the present study was to investigate the impact of lifestyle factors on BS and its dimensions, as well as on suicidal ideation among Spanish professionals dedicated to implant dentistry. Methods: A cross-sectional observational study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. An electronic survey based on the Maslach Burnout Inventory—Human Services Survey (MBI–HSS) was distributed to members of the Spanish Society of Implants. The data were analysed using descriptive statistical methods. Results: A total of 305 participants (20.9%) responded to the questionnaire. Notably, 10.8% of the professionals reported experiencing suicidal thoughts, a factor significantly associated with the presence of BS. The lifestyle factors associated with BS included the following: not engaging in aerobic exercise for at least 30 min per day (p < 0.05), not having hobbies that facilitate mental disconnection from work (p < 0.001), not following a balanced diet (p < 0.0001), having an insufficient social life (p < 0.0001), and experiencing suicidal ideation (p < 0.01). Conclusions: The surveyed dentists generally reported having healthy lifestyle habits. Nevertheless, one in ten professionals acknowledged having experienced suicidal ideation at some point, highlighting a concerning association with BS. Full article
(This article belongs to the Special Issue Mood Disorders: Diagnosis, Management and Future Opportunities)
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15 pages, 1624 KiB  
Article
Cytotoxicity Evaluation of Cyprodinil, Potentially Carcinogenic Chemical Micropollutant, for Oxidative Stress, Apoptosis and Cell Membrane Interactions
by Agata Jabłońska-Trypuć, Nina Wiśniewska, Gabriela Sitko, Urszula Wydro, Elżbieta Wołejko, Rafał Krętowski, Monika Naumowicz, Joanna Kotyńska, Marzanna Cechowska-Pasko, Bożena Łozowicka, Piotr Kaczyński and Adam Cudowski
Appl. Sci. 2025, 15(15), 8631; https://doi.org/10.3390/app15158631 (registering DOI) - 4 Aug 2025
Abstract
Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes [...] Read more.
Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes in the A-375 and DLD-1 cell lines was examined. The cell lines were selected because they can be an excellent in vitro model of neoplastic changes occurring in the skin and large intestine after exposure to a fungicide. The fungicide selected for the study is commonly used in Poland to protect crops against fungi. Our results showed that the tested compound increased cell viability and proliferation, probably activated by mechanisms related to oxidative stress. Cyprodinil caused an increase in glutathione level (in A-375 by about 37% and in DLD-1 by about 28%) and oxidative stress enzymes activity, but not in apoptosis level. Its membrane interactions and its penetration into cells was concentration dependent. It is worth emphasizing that the novelty of our work lies in the use of non-traditional toxicological methods based on molecular analyses using human cell lines. This allowed us to demonstrate not only the toxicity of a single substance but also its behavior within cellular structures. Our findings suggest that cyprodinil may have tumor-promoting properties in skin and colorectal cancer cells. Full article
(This article belongs to the Special Issue Exposure Pathways and Health Implications of Environmental Chemicals)
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27 pages, 1766 KiB  
Article
A Novel Optimized Hybrid Deep Learning Framework for Mental Stress Detection Using Electroencephalography
by Maithili Shailesh Andhare, T. Vijayan, B. Karthik and Shabana Urooj
Brain Sci. 2025, 15(8), 835; https://doi.org/10.3390/brainsci15080835 (registering DOI) - 4 Aug 2025
Abstract
Mental stress is a psychological or emotional strain that typically occurs because of threatening, challenging, and overwhelming conditions and affects human behavior. Various factors, such as professional, environmental, and personal pressures, often trigger it. In recent years, various deep learning (DL)-based schemes using [...] Read more.
Mental stress is a psychological or emotional strain that typically occurs because of threatening, challenging, and overwhelming conditions and affects human behavior. Various factors, such as professional, environmental, and personal pressures, often trigger it. In recent years, various deep learning (DL)-based schemes using electroencephalograms (EEGs) have been proposed. However, the effectiveness of DL-based schemes is challenging because of the intricate DL structure, class imbalance problems, poor feature representation, low-frequency resolution problems, and complexity of multi-channel signal processing. This paper presents a novel hybrid DL framework, BDDNet, which combines a deep convolutional neural network (DCNN), bidirectional long short-term memory (BiLSTM), and deep belief network (DBN). BDDNet provides superior spectral–temporal feature depiction and better long-term dependency on the local and global features of EEGs. BDDNet accepts multiple EEG features (MEFs) that provide the spectral and time-domain features of EEGs. A novel improved crow search algorithm (ICSA) was presented for channel selection to minimize the computational complexity of multichannel stress detection. Further, the novel employee optimization algorithm (EOA) is utilized for the hyper-parameter optimization of hybrid BDDNet to enhance the training performance. The outcomes of the novel BDDNet were assessed using a public DEAP dataset. The BDDNet-ICSA offers improved recall of 97.6%, precision of 97.6%, F1-score of 97.6%, selectivity of 96.9%, negative predictive value NPV of 96.9%, and accuracy of 97.3% to traditional techniques. Full article
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24 pages, 1861 KiB  
Review
Protective Effect of Melatonin Against Bisphenol A Toxicity
by Seong Soo Joo and Yeong-Min Yoo
Int. J. Mol. Sci. 2025, 26(15), 7526; https://doi.org/10.3390/ijms26157526 - 4 Aug 2025
Abstract
Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, is widely found in various consumer products and poses significant health risks, particularly through hormone receptor interactions, oxidative stress, and mitochondrial dysfunction. BPA exposure is associated with reproductive, metabolic, and neurodevelopmental disorders. Melatonin, a neurohormone with [...] Read more.
Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, is widely found in various consumer products and poses significant health risks, particularly through hormone receptor interactions, oxidative stress, and mitochondrial dysfunction. BPA exposure is associated with reproductive, metabolic, and neurodevelopmental disorders. Melatonin, a neurohormone with strong antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic agent to counteract the toxic effects of BPA. This review consolidates recent findings from in vitro and animal/preclinical studies, highlighting melatonin’s protective mechanisms against BPA-induced toxicity. These include its capacity to reduce oxidative stress, restore mitochondrial function, modulate inflammatory responses, and protect against DNA damage. In animal models, melatonin also mitigates reproductive toxicity, enhances fertility parameters, and reduces histopathological damage. Melatonin’s ability to regulate endoplasmic reticulum (ER) stress and cell death pathways underscores its multifaceted protective role. Despite promising preclinical results, human clinical trials are needed to validate these findings and establish optimal dosages, treatment durations, and safety profiles. This review discusses the wide range of potential uses of melatonin for treating BPA toxicity and suggests directions for future research. Full article
(This article belongs to the Section Molecular Toxicology)
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42 pages, 1407 KiB  
Review
Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes
by Charles F. Manful, Eric Fordjour, Dasinaa Subramaniam, Albert A. Sey, Lord Abbey and Raymond Thomas
Int. J. Mol. Sci. 2025, 26(15), 7520; https://doi.org/10.3390/ijms26157520 - 4 Aug 2025
Abstract
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. [...] Read more.
Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. Oxidative/nitrosative stress is a pathological state, resulting from the overproduction of reactive species exceeding the antioxidant capacity of the body, which is implicated in several chronic human diseases. Antioxidant therapies aimed at restoring redox balance and preventing oxidative/nitrosative stress have demonstrated efficacy in preclinical models. However, their clinical applications have met with inconsistent success owing to efficacy, safety, and bioavailability concerns. This summative review analyzes the role of reactive species in human pathophysiology, the mechanisms of action of antioxidant protection, and the challenges that hinder their translation into effective clinical therapies in order to evaluate potential emerging strategies such as targeted delivery systems, precision medicine, and synergistic therapeutic approaches, among others, to overcome current limitations. By integrating recent advances, this review highlights the value of targeting reactive species in the prevention and management of chronic diseases. Full article
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